Date of Award

Fall 2011

Document Type

Thesis

Degree Name

Master of Science in Biomedical Engineering - (M.S.)

Department

Biomedical Engineering

First Advisor

William C. Van Buskirk

Second Advisor

J. Christopher Fritton

Third Advisor

Treena Livingston Arinzeh

Abstract

Bone serves contradictory needs; bone must be strong yet light, and stiff yet flexible. At the tissue level bone material withstands cyclic loading without failing by dissipating energy via the formation and accumulation of microdamage. Proper removal of this damage in exchange for fresh tissue is vital to bone maintenance, and is achieved through a remodeling process. Imbalanced remodeling leads to osteoporotic fractures. Bisphosphonate drugs are proven to reduce fracture risk. However, the long-term effects of bisphosphonates on tissue-level properties are unknown. This study characterized the fatigue-life of cortical bone tissue after bisphosphonate treatment with alendronate (Aln). 1 1th ribs from 36 skeletally mature female beagles (1-2 years of age) treated daily with either a vehicle control (Cont, 1mL/kg saline) or Aln (0.2 or 1.0 mg/kg) for 3 years were evaluated. From both medial and lateral cortices, 1-6 cortical bone beams of uniform rectangular cross-section (0.5 x 1.5 mm) and length (10 - 12 mm) were prepared. A total of 90 bone beams were mechanically loaded in 4-point bending at specific stress amplitudes, 45- 85 MPa, applied sinusoidally at 2 Hz until fracture or 250,000 cycles. Compared to control, Aln 1.0 beams exhibited significantly lower initial stiffness (15%) and cycles to failure (>3-fold, p<0.05). While control exhibited increased loss of stiffness as a function of increasing stress amplitude, this was not observed with Aln treatment. This first fatigue study of bisphosphonate-treated bone suggests mechanisms behind the atypical cortical bone fracture patterns that have been observed clinically in a subset of patients on long-term bisphosphonate treatment.

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